Evidence is available to suggest that host genetics play a role in determining susceptibility to some bacterial infections and in determining the bacterial populations sustained within the human gastrointestinal tract. Colonic bacteria are involved in the metabolism and eneterohepatic recirculation of steroid hormones, as well as various phytochemicals, such as soy isoflavones. Elevated circulating levels of estrogens and an extended reproductive life as associated with increased risk of breast cancer. Factors that influence colonic function can modulate the metabolism the metabolism and excretion of steroid hormones and dietary chemopreventive agents, and therefore also may affect breast cancer risk. The capacity to produce equol from the soy isoflavone diadzein is a marker of inter-individual differences in clonic environment. The microflora capable of carrying out this metabolic step have yet to be identified; however, only about 30% of people are able to produce equol and few factors, except for antibiotics, alter this phenotype. Several studies suggest that the equol-producer phenotype may be associated with a lowered risk of breast cancer. Our overall research goal is to determine if there is a familial aggregation of the equol-producer phenotype and to identify the host genetics responsible for this phenotype. To this end, we propose to conduct a family-based phenotyping study to address: a) the possibility of a genetic determinant of the equol-producer phenotype; and b) the effects of age, sex, and environmental exposures on equol production. We will recruit 400 people (approximately 50-100 families with at least two generations in each family) and will phenotype each family member for equol- producer status. Participants will consume a standard dose of soy protein on three consecutive days and collect the first-void urine on the morning of the fourth day. Urinary equol-to-diadzein ratios will be used to establish equol-producer status. Correlation coefficients of the equol- producer phenotype will be estimated among family members, and the pattern formed will provide evidence as to whether one or more genetic factors are associated with this phenotype. This study could help to open a new area of research related to breast cancer susceptibility. If we can establish that the equol-producer phenotype is an inherited trait, we can then work to identify the associated genotype and determine more effectively whether this is a biomarker of breast cancer risk.